Iter-4360dd15-0003-transcript
第 3 轮执行轨迹
→ call search_memory({"limit":8,"query":"4360dd15 rapamycin human trial systematic review endpoints safety"})【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0002-transcript", "tags": "iteration transcript", "modified": "20260424173549000", "preview": "!! 第 2 轮执行轨迹
→ ca"}, {"title": "Iter-4360dd15-0001-transcript", "tags": "iteration transcript", "modified": "20260424173243000", "preview": "!! 第 1 轮执行轨迹 4360dd15 起始时间：2026-04-25T01:22:08 !! 使用说明 这是 Sisyphus 的北极星。永远围绕这个目标展开。 其它 mis"}, {"title": "Rapamycin human trials: extracted endpoints and outcomes from the 2024 systematic review review pass 1", "tags": "knowledge fact experiment 4360dd15", "modified": "20260424173529000", "preview": "!! Rapamycin human trial evidence from a 2024 systematic review This round I narrowed the long-longevity question to a single mechanism: rapamycin / mTOR. → call list_recent({"n":6})
【tool:list_recent】
{"ok": true, "items": [{"title": "Iter-4360dd15-0002-reflection", "modified": "20260424173558000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424173558000", "tags": "pinned focus"}, {"title": "先抓人类试验证据表", "modified": "20260424173558000", "tags": "lesson evidence human-trials rapamycin"}, {"title": "Iter-4360dd15-0002-transcript", "modified": "20260424173549000", "tags": "iteration transcript"}, {"title": "Rapamycin human trials: extracted endpoints and outcomes from the 2024 systematic review review pass 1", "modified": "20260424173529000", "tags": "knowledge fact experiment 4360dd15"}, {"title": "Iter-4360dd15-0001-reflection", "modified": "20260424173249000", "tags": "iteration reflection"}]}
→ call read_note({"title":"NEXT_FOCUS"})
【tool:read_note】
{"ok": true, "title": "NEXT_FOCUS", "tags": "pinned focus", "text": "!! 下轮焦点（来自 mission 4360dd15 · Iter-0002）\n\n下一轮只攻克一个最窄问题：拿到 rapamycin 人类试验的具体纳入列表、主要终点和安全性结论。"}
→ call web_search({"limit":5,"query":"\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\" full text abstract trial list"})
→ call web_search({"limit":5,"query":"site:pubmed.ncbi.nlm.nih.gov rapamycin humans systematic review 2024 Lee Hodzic Kuerec Maier"})
→ call web_search({"limit":5,"query":"site:vu.nl rapamycin humans systematic review PDF Lee Hodzic Kuerec Maier"})
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\" full text abstract trial list", "results": [{"title": "The Lancet | The best science for better lives", "url": "https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/ppt", "snippet": "Targeting ageing with rapamycin and its derivatives in humans: a systematic review"}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.researchgate.net/publication/377976071_Targeting_ageing_with_rapamycin_and_its_derivatives_in_humans_a_systematic_review", "snippet": "Request PDF | On Feb 1, 2024, Deborah J W Lee and others published Targeting ageing with rapamycin and its derivatives in humans: a systematic review | Find, read and cite all the research you ..."}]}
【tool:web_search】
{"ok": true, "query": "site:pubmed.ncbi.nlm.nih.gov rapamycin humans systematic review 2024 Lee Hodzic Kuerec Maier", "results": [{"title": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/", "snippet": "PubMed® comprises more than 40 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full text content from PubMed Central and publisher web sites ."}, {"title": "Advanced Search Results - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/advanced/", "snippet": "Advanced Search Results - PubMed Your history is currently empty! As you use PubMed your recent searches will appear here."}, {"title": "The bioavailability and blood levels of low-dose rapamycin for ...", "url": "https://pubmed.ncbi.nlm.nih.gov/39873920/", "snippet": "Rapamycin , also known as sirolimus, has demonstrated great potential for application in longevity medicine. However, the dynamics of low-dose rapamycin bioavailability, and any differences in bioavailability for different formulations (e.g., compounded or commercial), remain poorly understood."}, {"title": "A Systematic Review of the Efficacy and Safety of Sirolimus ... - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/41368601/", "snippet": "Objective: The use of rapamycin (sirolimus) in the treatment of infantile hemangioma (IH) is a persistent challenge in dermatology. We aim to systematically review the efficacy and safety of rapamycin for IH treatment. Methods: We systema
【tool:web_search】
{"ok": true, "query": "site:vu.nl rapamycin humans systematic review PDF Lee Hodzic Kuerec Maier", "results": []}
→ call read_note({"title":"Rapamycin human trials: extracted endpoints and outcomes from the 2024 systematic review review pass 1"})
【tool:read_note】
{"ok": true, "title": "Rapamycin human trials: extracted endpoints and outcomes from the 2024 systematic review review pass 1", "tags": "knowledge fact experiment 4360dd15", "text": "!! Rapamycin human trial evidence from a 2024 systematic review\nThis round I narrowed the long-longevity question to a single mechanism: rapamycin / mTOR.\n\n!! Source\nTargeting ageing with rapamycin and its derivatives in humans: a systematic review (Lee, Hodzic Kuerec, Maier), Lancet Healthy Longevity 2024; 5(2):e152-e162. The VU repository page includes the abstract and full bibliographic metadata.\n\n!! Extracted human trial snapshot\nThe review reports: 18,400 unique records screened, 19 included studies. Benefits were seen mainly in immune, cardiovascular, and integumentary systems; no significant effects in endocrine, muscular, or neurological systems.\n\n| Study | Population | Agent | Dose / schedule | Design | Primary endpoint | Result |\n|---|---|---|---|---|---|---|\n| Krebs et al. 2007 | 11 men, 28 +/- 1 y | rapamycin | 6 mg single dose | randomized, double-blind, placebo-controlled, crossover | peripheral insulin sensitivity during insulin clamp + amino acid infusion | met |\n| Drummond et al. 2009 | 15 men, 29 +/- 2 y | rapamycin | 12 mg single dose 2 h before resistance exercise | acute exercise +/- rapamycin | post-exercise mixed-muscle protein synthesis | met |\n| Gunderman 2014 | 16 men, 26 +/- 1 y | rapamycin | 16 mg single dose 1 h before blood-flow-restricted re
→ call web_fetch({"max_chars":6000,"url":"https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext"})
→ call web_fetch({"max_chars":6000,"url":"https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/ppt"})
→ call web_search({"limit":8,"query":"\"PIIS2666-7568(23)00258-1\" rapamycin full text"})
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/ppt'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
【tool:web_search】
{"ok": true, "query": "\"PIIS2666-7568(23)00258-1\" rapamycin full text", "results": []}
→ call pubmed_search({"limit":5,"query":"\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\""})
【tool:pubmed_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\"", "results": [{"pmid": "38310895", "title": "Targeting ageing with rapamycin and its derivatives in humans: a systematic review.", "source": "Lancet Healthy Longev", "pubdate": "2024 Feb", "authors": ["Lee DJW", "Hodzic Kuerec A", "Maier AB"], "url": "https://pubmed.ncbi.nlm.nih.gov/38310895/"}, {"pmid": "28504837", "title": "Immunotherapy for metastatic renal cell carcinoma.", "source": "Cochrane Database Syst Rev", "pubdate": "2017 May 15", "authors": ["Unverzagt S", "Moldenhauer I", "Nothacker M", "Roßmeißl D", "Hadjinicolaou AV", "Peinemann F", "Greco F", "Seliger B"], "url": "https://pubmed.ncbi.nlm.nih.gov/28504837/"}]}
→ call web_fetch({"max_chars":7000,"url":"https://pubmed.ncbi.nlm.nih.gov/38310895/"})
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://pubmed.ncbi.nlm.nih.gov/38310895/'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
→ call web_search({"limit":8,"query":"38310895 rapamycin review abstract safety adverse events rapamycin humans"})
→ call web_search({"limit":8,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" adverse events safety abstract"})
→ call web_search({"limit":8,"query":"\"38310895\" \"rapamycin\" adverse events"})
【tool:web_search】
{"ok": true, "query": "38310895 rapamycin review abstract safety adverse events rapamycin humans", "results": [{"title": "Influence of rapamycin on safety and healthspan metrics after one year ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12074816/", "snippet": "An important gap in the clinical understanding of rapamycin for longevity is that to date, no long-term randomized controlled trials (RCT) have been conducted to explore the safety and effectiveness of low-dose, intermittent rapamycin regimens for improving multiple healthspan metrics in normative aging cohorts."}, {"title": "Influence of rapamycin on safety and healthspan metrics after one year ...", "url": "https://www.aging-us.com/article/206235/pdf", "snippet": "ABSTRACT Design: This 48-week decentralized, double-blinded, randomized, placebo-controlled trial (NCT04488601) evaluated the long-term safety of intermittent low-dose rapamycin in a healthy, normative-aging human cohort. Participants received placebo, 5 mg or 10 mg compounded rapamycin weekly."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext", "snippet": "No serious adverse events attributed to rapamycin and its derivatives were reported in healthy individuals; however, there were increased numbers of infections and increases in total cholesterol, LDL cholesterol, and triglycerides in individuals with ageing-related disea
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" adverse events safety abstract", "results": [{"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext", "snippet": "Rapamycin and its derivatives (rapalogs) are inhibitors of mTOR, a major regulator of the ageing process. We aimed to summarise the effects of rapamycin and its derivatives on the severity of ageing-related physiological changes and disease in adults. A search across five databases yielded 18 400 unique articles, resulting in 19 included studies. Rapamycin and its derivatives improved ..."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.researchgate.net/publication/377976071_Targeting_ageing_with_rapamycin_and_its_derivatives_in_humans_a_systematic_review", "snippet": "Request PDF | On Feb 1, 2024, Deborah J W Lee and others published Targeting ageing with rapamycin and its derivatives in humans : a systematic review | Find, read and cite all the research you ..."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://findanexpert.unimelb.edu.au/scholarlywork/1860397-targeting-ageing-with-rapamycin-and-its-derivatives-in-humans--a-systematic-review", "snippet": "Abstract Rapamycin and its derivatives (rapalogs) are inhibitors of mTOR, a major regulator of the ag
【tool:web_search】
{"ok": true, "query": "\"38310895\" \"rapamycin\" adverse events", "results": []}
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" trial table included studies"})
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" Krebs Drummond Gundermann Mannick Kraig Chung RTB101"})
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" trial table included studies", "results": [{"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext", "snippet": "A search across five databases yielded 18 400 unique articles, resulting in 19 included studies . Rapamycin and its derivatives improved physiological parameters associated with ageing in the immune, cardiovascular, and integumentary systems of healthy individuals or individuals with ageing-related diseases."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.sciencedirect.com/science/article/pii/S2666756823002581", "snippet": "A search across five databases yielded 18 400 unique articles, resulting in 19 included studies . Rapamycin and its derivatives improved physiological parameters associated with ageing in the immune, cardiovascular, and integumentary systems of healthy individuals or individuals with ageing-related diseases."}, {"title": "PDF Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.thelancet.com/pdfs/journals/lanhl/PIIS2666-7568(23)00258-1.pdf", "snippet": "A search across five databases yielded 18 400 unique articles, resulting in 19 included studies . Rapamycin and its derivatives improved physiological parameters associated with ageing in the immune,
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" Krebs Drummond Gundermann Mannick Kraig Chung RTB101", "results": [{"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.sciencedirect.com/science/article/pii/S2666756823002581", "snippet": "Rapamycin and its derivatives (rapalogs) are inhibitors of mTOR, a major regulator of the ageing process. We aimed to summarise the effects of rapamycin and its derivatives on the severity of ageing-related physiological changes and disease in adults. A search across five databases yielded 18 400 unique articles, resulting in 19 included studies. Rapamycin and its derivatives improved ..."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext", "snippet": "Rapamycin and its derivatives (rapalogs) are inhibitors of mTOR, a major regulator of the ageing process. We aimed to summarise the effects of rapamycin and its derivatives on the severity of ageing-related physiological changes and disease in adults. A search across five databases yielded 18 400 unique articles, resulting in 19 included studies. Rapamycin and its derivatives improved ..."}, {"title": "PDF Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.thelancet.com/pdfs/journals/lanhl/PIIS2666-7568(23)00258-1.pdf", "snippet": "Deborah J W
→ call web_fetch({"max_chars":7000,"url":"https://research.vu.nl/en/publications/targeting-ageing-with-rapamycin-and-its-derivatives-in-humans-a-s"})
【tool:web_fetch】
{"ok": true, "url": "https://research.vu.nl/en/publications/targeting-ageing-with-rapamycin-and-its-derivatives-in-humans-a-s/", "status": 200, "content_type": "text/html;charset=UTF-8", "text": "Targeting ageing with rapamycin and its derivatives in humans: a systematic review - Vrije Universiteit Amsterdam Skip to main navigation Skip to search Skip to main content Vrije Universiteit Amsterdam Home Help & FAQ Link opens in a new tab Search content at Vrije Universiteit Amsterdam Home Profiles Research units Research output Courses Projects Datasets / Software Activities Prizes / Grants Press / Media Targeting ageing with rapamycin and its derivatives in humans: a systematic review Deborah J W Lee , Ajla Hodzic Kuerec , Andrea B Maier Prevention and Rehabilitation AMS - Ageing & Vitality APH - Aging & Later Life APH - Global Health Research output : Contribution to Journal › Review article › Academic › peer-review Overview Fingerprint Abstract Rapamycin and its derivatives (rapalogs) are inhibitors of mTOR, a major regulator of the ageing process. We aimed to summarise the effects of rapamycin and its derivatives on the severity of ageing-related physiological changes and disease in adults. A search across five databases yielded 18 400 unique articles, resulting in 19 included studies. Rapamycin and its derivatives improved physiological parameters associated with ageing in the immune, cardiovascular, and integumentary systems of healthy individuals or individuals with agein
→ call web_fetch({"max_chars":7000,"url":"https://europepmc.org/article/MED/38310895"})
【tool:web_fetch】
{"ok": true, "url": "https://europepmc.org/article/MED/38310895", "status": 200, "content_type": "text/html;charset=UTF-8", "text": "Europe PMC Europe PMC 1 Sign in | Create an account https://orcid.org https://plus.europepmc.org Europe PMC Menu About About Europe PMC Preprints in Europe PMC Funders Become a funder Governance Roadmap Outreach Tools Tools overview Article status monitor Grant finder External links service RSS feeds About SciLite annotations Annotations submission service Developers Developer resources Articles RESTful API Grants RESTful API API case studies SOAP web service Annotations API OAI service Bulk downloads Developers Forum Support User guide Search syntax guide Contact us Contact us Helpdesk Feedback Twitter Blog Tech blog Developer Forum Europe PMC plus NOTICE: The ORCID Claiming tool has been temporarily disabled, because of technical issues. Please check back in later.", "truncated": false}
→ call web_search({"limit":10,"query":"site:clinicaltrials.gov rapamycin aging humans NCT04488601 trial rapamycin weekly 5 mg 10 mg"})
→ call web_search({"limit":10,"query":"site:clinicaltrials.gov everolimus vaccine response aging trial 2014 Mannick"})
→ call web_search({"limit":10,"query":"site:clinicaltrials.gov topical rapamycin skin aging Chung 2019 trial"})
【tool:web_search】
{"ok": true, "query": "site:clinicaltrials.gov rapamycin aging humans NCT04488601 trial rapamycin weekly 5 mg 10 mg", "results": [{"title": "Participatory Evaluation (of) Aging (With) Rapamycin (for) Longevity ...", "url": "https://clinicaltrials.gov/study/NCT04488601", "snippet": "Details for study NCT04488601 , | ClinicalTrials.gov A randomized, double-blind, placebo-controlled trial assessing the effects of low and high doses of intermittent Rapamycin on a weekly schedule. The researchers aim to establish a long-term safety profile, determine the long-term efficacy of Rapamycin in reducing clinical aging measures, and biochemical and physiological endpoints associated ..."}, {"title": "Effect of mTOR Inhibition & Other Metabolism Modulating Interventions ...", "url": "https://clinicaltrials.gov/study/NCT04742777", "snippet": "Investigators are conducting a translational trial to test whether rapamycin also improves life functions in humans focusing on elderly persons (aged 70-95). Substudy E will evaluate the Rapamycin and Cardiac Function."}, {"title": "PDF (Rapamycin inhibition of DDSP [RID]) - ClinicalTrials.gov", "url": "https://cdn.clinicaltrials.gov/large-docs/01/NCT02565901/Prot_SAP_000.pdf", "snippet": "Phase 1 This is a dose finding scheme, where dose groups will be enrolled with a target of up to six (no less than three) patients per dose. Groups will be treated with de-escalating doses of Sirolimus combined with a fixed dose of docetaxel and carboplatin (60 mg /
【tool:web_search】
{"ok": true, "query": "site:clinicaltrials.gov everolimus vaccine response aging trial 2014 Mannick", "results": [{"title": "NCT05835999 | Everolimus Aging Study - ClinicalTrials.gov", "url": "https://clinicaltrials.gov/study/NCT05835999", "snippet": "Using a double-blinded, randomized, placebo-controlled clinical trial , the investigators will perform a battery of gold-standard and innovative techniques to test the hypothesis that daily low dose or weekly everolimus treatment will improve 4 inter-related domains of physiological aging : metabolic, cardiac, cognitive, and physical function."}, {"title": "Trial of Paclitaxel/ Bevacizumab +/ - Everolimus for Patients With HER2 ...", "url": "https://clinicaltrials.gov/study/NCT00915603", "snippet": "This randomized, double blind, placebo controlled trial will evaluate the impact of adding everolimus to the combination of weekly paclitaxel plus bevacizumab in the first-line treatment of women with HER2-negative metastatic breast cancer."}, {"title": "Study Details | PREPARE-iVAC Trial | ClinicalTrials.gov", "url": "https://clinicaltrials.gov/study/NCT05924685", "snippet": "Official Title Prospective Randomized Trial of Everolimus Replacing MMF/MP Acid by the RECOVAC Consortium to Increase VACcine Response in Kidney Transplant Patients"}, {"title": "PDF A phase IIIb, multi-center, open-label study of EVERolimus (RAD001) in ...", "url": "https://cdn.clinicaltrials.gov/large-docs/38/NCT03176238/Prot_001.pdf", "snippet": "Everolimus
【tool:web_search】
{"ok": true, "query": "site:clinicaltrials.gov topical rapamycin skin aging Chung 2019 trial", "results": []}
→ call web_search({"limit":8,"query":"\"Influence of rapamycin on safety and healthspan metrics after one year\" abstract safety adverse events placebo 5 mg 10 mg"})
→ call web_search({"limit":8,"query":"site:pmc.ncbi.nlm.nih.gov \"Influence of rapamycin on safety and healthspan metrics after one year\""})
→ call web_search({"limit":8,"query":"site:aging-us.com \"Influence of rapamycin on safety and healthspan metrics after one year\""})
【tool:web_search】
{"ok": true, "query": "\"Influence of rapamycin on safety and healthspan metrics after one year\" abstract safety adverse events placebo 5 mg 10 mg", "results": []}
【tool:web_search】
{"ok": true, "query": "site:pmc.ncbi.nlm.nih.gov \"Influence of rapamycin on safety and healthspan metrics after one year\"", "results": []}
【tool:web_search】
{"ok": true, "query": "site:aging-us.com \"Influence of rapamycin on safety and healthspan metrics after one year\"", "results": []}
【assistant】
本轮结论（可验证）：
1. **2024 综述已确认是我们该盯的主证据源**
- 论文：**Targeting ageing with rapamycin and its derivatives in humans: a systematic review**
- 作者：Lee / Hodzic Kuerec / Maier
- 期刊：**The Lancet Healthy Longevity** 2024; 5(2): e152–e162
- VU 公开页的摘要可直接读到关键信息，绕开了 Lancet / PubMed 的 403 问题。
2. **这篇综述的系统级结论很明确**
- 检索了 **18,400** 条唯一记录
- 最终纳入 **19 项研究**
- **在人类中**，rapamycin / rapalogs 对：
- **免疫系统**
- **心血管系统**
- **皮肤/整合系统**
```